Domestic cats are subject to infection by several retroviruses, including feline leukemia virus (FeLV), feline sarcoma virus (FeSV), endogenous type C oncoronavirus (RD-114), and feline syncytia-forming virus (FeSFV). Of these, FeLV is the most significant pathogen, causing diverse symptoms including lymphoreticular and myeloid neoplasms, anemias, immune-mediated disorders, and an immunodeficiency syndrome that is similar to human acquired immune deficiency syndrome (AIDS). Recently, a particular replication-defective FeLV mutant, designated FeLV-AIDS, has been more particularly associated with immunosuppressive properties.
The discovery of feline T-lymphotropic lentivirus (now designated as feline immunodeficiency virus, FIV) was first reported in Pedersen et al. (1987). Characteristics of FIV have been reported in Yamamoto et al. (1988a); Yamamoto et al. (1988b); and Ackley et al. (1990). Seroepidemiologic data have shown that infection by FIV is indigenous to domestic and wild felines throughout the world. A wide variety of symptoms are associated with infection by FIV, including abortion, alopecia, anemia, conjunctivitis, chronic rhinitis, enteritis, gingivitis, hematochezia, neurologic abnormalities, periodontitis, and seborrheic dermatitis. The immunologic hallmark of domestic cats infected with FIV is a chronic and progressive depletion of feline CD4+ peripheral blood lymphocytes, a reduction in the CD4:CD8 cell ratio and, in some cases, an increase in CD8-bearing lymphocytes. Based on molecular, biochemical and immunopathologic characteristics, FIV infection of cats is now considered to be a better feline AIDS model than FeLV-FAIDS.
Cloning and sequence analysis of FIV has been reported in Olmsted et al. (1989a); Olmsted et al. (1989b); and Talbott et al. (1989). Hosie and Jarret (1990) described the serological response of cats infected with FIV. FIV virus subtypes can be classified according to immunotype based on the level of cross-neutralizing antibodies elicited by each strain (Murphy and Kingsbury, 1990). Recently, viruses have been classified into subtypes according to genotype based on nucleotide sequence homology. Although HIV and FIV subtyping is based on genotype (Sodora et al., 1994; Rigby et al., 1993; and Louwagie et al., 1993), little is known about the correlation between the genotype and immunotype of subtypes. FIV viral isolates are currently classified into four FIV subtypes: A, B, C and D. (Kakinuma et al., 1995). The following abbreviations of FIV strains are used herein:
Strain (subtype)AbbreviationPetaluma (A)FIVPetDixon (A)FIVDixUK8 (A)FIVUK8Bangston (B)FIVBangAomori-1 (B)FIVAom1Aomori-2 (B)FIVAom2Shizuoka (D)FIVShiInfectious isolates and infectious molecular clones have been described for all FIV subtypes except for subtype C (Sodora et al., 1994). Subtype C FIV has only been identified from cellular DNA of cats from Canada (Sodora et al., 1994; Rigby et al., 1993; Kakinuma et al., 1995).
To date, there have been no reported cases of retroviral zoonosis between domestic cats and humans (Pedersen et al., 1987; Yamamoto et al., 1989; Yamamoto et al., 1988; Butera et al., 2000; CDC Report: HIV and Retrovirology). No cases of feline leukemia virus (FeLV), feline foamy virus (FeFV), and feline immunodeficiency virus (FIV) infections of humans have been reported, even in populations at high risk for viral exposure, such as veterinarians, animal caretakers, and scientists from feline retroviral laboratories (Yamamoto et al. 1989; Yamamoto et al., 1988; Butera et al., 2000). Human patients with leukemia and chronic fatigue syndrome selected for their disease association also tested negative for FeLV (Butera et al., 2000). However, many of the assays used in these studies were based on less sensitive antigen and antibody tests (Butera et al., 2000). In few of these studies, a more sensitive FeLV PCR (polymerase chain reaction) system for proviral DNA and a sensitive Western blot analysis for FIV antibodies were performed but their findings also supported previous reports of the lack of feline retroviral zoonosis (Yamamoto et al. 1988; Butera et al., 2000). In vitro studies have shown that all three of these feline retroviruses are capable of infecting primary human cells and human cell (Butera et al., 2000; Sarma et al., 1970; Azocar et al., 1979; Jarrett et al., 1973). Recent studies have also demonstrated that HIV infects human cells in vitro via the CXCR4 receptor, which has been shown to be a coreceptor for HIV-1 (Willett et al., 1997a; Willett et al., 1997b; Poeschla et al., 1998; Richardson et al., 1999; Johnston et al., 1999b). It has been reported that FIV vector sequences which included FIV rev-RRE and gag are more efficient in infecting human cells than those without FIV gag (Johnston et al., 1999).
Zoonotic infection of humans with SIV has been limited to individuals working with SIV or SIV-infected laboratory animals (Khabbaz et al, 1994; Khabbaz et al., 1992). All of the SIV-infected individuals are clinically asymptomatic with one having transient infection while the other showed persistent infection.
Disclosed herein is the surprising discovery of zoonotic retroviral infection of humans in vivo with FIV. It has also been discovered that zoonotic HIV infection can complicate the current HIV-1 antibody diagnostic tests that are used commercially to screen persons for infection with HIV.